Aldols (.beta.-hydroxy- and .beta.-alkoxy aldehydes) are useful chemical compounds used in the manufacture of antibiotics and other medicinal compounds, and in various natural products syntheses. The carboxylic acid analogs of certain chiral aldols have been used in liquid crystal applications.
Typically, aldols are prepared by an aldol condensation reaction. For example, the compound named "aldol" (.beta.-hydroxybutyraldehyde) is prepared by condensation of acetaldehyde in sodium hydroxide solution. Schematically, an aldol condensation is expressed by the equation: ##STR1##
Over the years, a large amount of chemistry has been developed to produce aldol products with high diastereomeric and enantiomeric control. The following reviews are illustrative: Heathcock, C. H. "The Aldol Addition Reaction," in Asymmetric Synthesis; Morrison, J. D., Ed.; Academic Press: New York, 1984; Vol. 3, Ch.2, pp 111-212; Braun, M. "Recent Developments in Stereoselective Aldol Reactions," in Advances in Carbanion Chemistry, Snieckus, V., Ed.; Jai Press: Greenwich, Conn., 1992; Vol. 1, Ch. 4; Togni, A.; Pastor, S. D. Chirality 1991, 3,331; Evans, D. A.; Nelson, J. V.; Taber, T. R. Top. Stereochem. 1982, 13,1; and Masamune, S.; Choy, W. Aldrichim. Acta 1982, 15,47. For some recent specific examples, see: Paterson, I.; Lister, M. A.; McClure, C. K. Tetrahedron Lett. 1986, 27,4787 and references therein; and Reetz, M. T.; Kunisch, F.; Heitman, P. Tetrahedron Lett. 1986,27,4721.
In general, the known methods for enantiocontrol utilize an aldol reaction with well-designed chiral auxiliaries to produce the desired enantiomers with, at times, quite high selectivity. A few exceptions to this generalization are known, however. In a series of papers, Yamamoto has shown that hindered aluminum-based Lewis acids can promote rearrangements of epoxy silyl ethers to produce various products, including both erythro and threo aldols. See Maruoka, K.; Sato, J.; Yamamoto, H. Tetrahedron 1992, 48, 3749; Maruoka, K.; Ooi, T.; Yamamoto, H. J. Am. Chem. Soc. 1989, 111, 6431; and Maruoka, K.; Ooi, T.; Nagahara S.; Yamamoto, H. Tetrahedron 1991, 47, 6983. In each case, however, the group being transferred is originally attached to the epoxide carbon, and not to the adjacent carbon (the carbon that becomes the C.sub.2 position, .alpha. to the aldehyde).
Tsuchihashi has observed transfer of alkyl groups from adjacent carbons to tertiary epoxide centers to generate quaternary carbons .alpha. to ketones, but has not reported the preparation of tertiary centers or aldehydes by that approach. See Maruoka, K.: Hagesawa, M.; Yamamoto, H.; Suzuki, K.; Shimazaki, M.; Tsuchihashi, G. J. Am. Chem. Soc. 1986, 108, 3827; Suzuki, K.; Miyazawa, M.; Tsuchihashi, G. Tetrahedron Lett. 1987, 28 3515; and Shimazaki, M.; Hara, H.; Suzuki, K.; Tsuchihashi, G. Tetrahedron Lett. 1987, 28, 5891.
In a joint paper, Tsuchihashi and Yamamoto reported the migration of phenyl and vinyl groups in the presence of TiCl.sub.4 and Et.sub.3 SiH to produce primary alcohols. See J.Am. Chem. Soc. 1986, 108, 3827.
Despite the success of such methods, however, the preparation of particular aldols having specific stereoconfigurations at the C.sub.2 and C.sub.3 positions can be problematic. Thus, new, stereoselective routes to aldols, particularly 2-alkyl-3-silyloxyalkanals and 2-alkyl-3-hydroxyalkanals, are desired.